title: Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole.
abstract: Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L(-1) to 88 mg • L(-1) with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL(-1), respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors.forename: Xiao-juan
authors.initials: XJ
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Zhou
authors.forename: Qiao-ling
authors.initials: QL
authors.lastname: Zhu
authors.forename: Yong-yan
authors.initials: YY
authors.lastname: Bei
authors.forename: Ben-gang
authors.initials: BG
authors.lastname: You
authors.forename: Chun-ge
authors.initials: CG
authors.lastname: Zhang
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Chen
authors.forename: Zhou-li
authors.initials: ZL
authors.lastname: Wang
authors.forename: Ai-jun
authors.initials: AJ
authors.lastname: Zhu
authors.forename: Xue-nong
authors.initials: XN
authors.lastname: Zhang
authors.forename: Yu-jiang
authors.initials: YJ
authors.lastname: Fan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003374:Coumarins / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D004058:Diffusion; D004339:Drug Compounding; D006801:Humans; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D010316:Particle Size; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D008823:Micelles; D053769:Nanocapsules; D048271:Chitosan; C046627:osthol
keywords: N-trimethyl chitosan; antitumor activity; micelle solubilization